Unique compounds useful for inhibiting a proteasome in a cell, pharmaceutical compositions and methods of their use are provided herein.

There is described herein, multimers comprising a plurality of compounds covalently linked together, the compounds independently being of formula (I). ##STR00001##

Compounds with the following structures ##STR00001##
and their analogs are provided. Compositions that include these structures can be used to inhibit glucose transporters and stop or decrease the proliferation of cancer, treat possible organ rejection and treat autoimmune disease.

The present invention generally relates to compounds that are useful for inhibiting one or more trypsin-like S1 serine proteases, HGFA, matriptase, hepsin, KLK5 and/or TMPRSS2 as well as cysteine proteases including trypsin-like cysteine proteases (e.g. Cathepsin B). The present invention also relates to various methods of using the inhibitor compounds to treat or prevent viral infections, including those caused by coronaviruses and influenza, conditions associated with KLK5, various malignancies, pre-malignant conditions, and cancer.

The invention relates to cyclic peptide agonists that bind to the mu (morphine) opioid receptor and their use in the treatment of acute and/or chronic pain. Embodiments of the invention are directed to cyclic pentapeptide and hexapeptide analogs of endomorphin that have (i) a carboxy-terminal extension with an amidated hydrophilic amino acid and (ii) a substitution in amino acid position 2, and in some embodiments, a 2′,6′-dimethyltyrosine (Dmt) residue in place of the N-terminal tyrosine residue a position 1. These peptide analogs exhibit increased solubility compared to similar tetrapeptide analogs while maintaining favorable or improved therapeutic ratios of analgesia to side effects.

The present invention provides methods of making α4β7 peptide monmer and dimer antagonists. Methods of the present invention include solid phase and solution phase methods, as well as synthesis via condensation of smaller peptide fragments. Methods of the present invention further include methods directed to the synthesis of peptides comprising one or more penicillamine residues.

Provided is a cyclic peptide derivative which is derived from Paecilomyces tenuipes having an astrocyte proliferative activity, or a salt thereof.

Cyclic tetrapeptide stereochemical isomers of CJ-15,208, pharmaceutical compositions from such cyclic tetrapeptides, and methods of using such pharmaceutical compositions. The cyclic tetrapeptide compounds and pharmaceutical compositions disclosed herein are potent analgesics active in several pain models with generally minimal tolerance and reduced likelihood to induce addiction relative to other known opiates.

Disclosed are compounds having enhanced potency in the modulation of NMD A receptor activity. Such compounds are contemplated for use in the treatment of diseases and disorders, such as learning, cognitive activities, and analgesia, particularly in alleviating and/or reducing neuropathic pain. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.

The present invention relates to cyclic amino acid molecules and methods of preparing the same, and in particular the macrocyclization of amino acids or linear peptides bound to a solid support.